Choline Fenofibrate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Choline Fenofibrate contains NLT 97.0% and NMT 103.0% of choline fenofibrate (C₁₇H₁₄ClO₄⁻ · C₅H₁₄NO⁺), calculated on the anhydrous basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉, Infrared Spectroscopy: 197A

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C.

Mobile phase: 18 mM methanesulfonic acid in water

Standard stock solution: Equivalent to 500 μg/mL of choline in water from USP Choline Chloride RS

Standard solution: Equivalent to 100 μg/mL of choline in Mobile phase from Standard stock solution

Sample stock solution: 2 mg/mL of Choline Fenofibrate in water

Sample solution: 0.4 mg/mL of Choline Fenofibrate in Mobile phase from Sample stock solution. [NOTE—This solution has an approximate concentration of 100 µg/mL of choline.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: Ion chromatography

Detector: Conductivity with a suitable suppressor Column: 4.0-mm × 25-cm; 8-μm packing L106

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The retention time of the choline peak of the Sample solution corresponds to the retention time of the choline peak of the Standard solution.

3 ASSAY

3.1 PROCEDURE

Protect solutions containing fenofibric acid or choline fenofibrate from light. Solution A: Water adjusted with phosphoric acid to a pH of 2.5

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Solution A and Solution B (50:50)

Standard stock solution: 0.5 mg/mL of USP Fenofibric Acid RS in acetonitrile

Standard solution: 100 µg/mL of USP Fenofibric Acid RS in Diluent from the Standard stock solution

Sample solution: 130 µg/mL of Choline Fenofibrate in Diluent

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 286 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 40 µL

3.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.10%

3.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of choline fenofibrate (C₁₇H₁₄ClO₄⁻ · C₅H₁₄NO⁺) in the portion of Choline Fenofibrate taken:

Result = (r_u/r_s) × (C_s/C_u) × (M_r1/M_r2) × 100

r_u = peak response of fenofibric acid from the Sample solution

r_s = peak response of fenofibric acid from the Standard solution

C_s = concentration of USP Fenofibric Acid RS in the Standard solution (µg/mL)

C_u = concentration of Choline Fenofibrate in the Sample solution (µg/mL)

M_r1 = molecular weight of choline fenofibrate, 421.91

M_r2 = molecular weight of fenofibric acid, 318.75

Acceptance criteria: 97.0%–103.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION 〈281〉

NMT 0.15%

4.2 ORGANIC IMPURITIES

Protect solutions containing fenofibric acid or choline fenofibrate from light.

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution: 500 µg/mL of USP Fenofibric Acid RS, and 200 µg/mL each of USP Fenofibrate RS and USP Fenofibrate Related Compound C RS in acetonitrile

System suitability solution: 5 µg/mL of USP Fenofibric Acid RS, and 2 µg/mL each of USP Fenofibrate RS and USP Fenofibrate Related Compound C RS in Diluent from System suitability stock solution. Expose the solution to high intensity UV light with an intensity of NLT 650 foot-candles for approximately 2 min. Fenofibric acid will degrade to generate an unknown light degradation product having a relative retention time of 0.93.

Standard solution: 1 µg/mL of USP Fenofibric Acid RS in Diluent

Sensitivity solution: 0.05 µg/mL of USP Fenofibric Acid RS in Diluent from the Standard solution

4.2.1 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 2.0 between unknown light degradation product (RRT 0.93) and fenofibric acid (1.0), System suitability solution Relative standard deviation: NMT 3.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.2.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity and any unspecified impurity in the portion of Choline Fenofibrate taken:

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × (M_r1/M_r2) × 100

r_u = peak response of each specified impurity or any unspecified impurity from the Sample solution

r_s = peak response of fenofibric acid from the Standard solution

C_s = concentration of USP Fenofibric Acid RS in the Standard solution (µg/mL)

C_u = concentration of Choline Fenofibrate in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of choline fenofibrate, 421.91

M_r2 = molecular weight of fenofibric acid, 318.75

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

WATER DETERMINATION 〈921〉 , Method I, Method Ia: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers and store below 30°.

USP REFERENCE STANDARDS 〈11〉

USP Choline Chloride RS USP Choline Fenofibrate RS USP Fenofibrate RS

USP Fenofibric Acid RS

2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid.

USP Fenofibrate Related Compound C RS

1-Isopropoxy-2-methyl-1-oxopropan-2-yl  2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate.